The objective of this proposal is to develop a percutaneous respiratory assist catheter (PRAC) that can be inserted into the venous system to provide supplemental breathing support, independent of the lungs, for patients requiring short- term (less than 1-2 weeks) respiratory assistance. The PRAC will be designed for percutaneous insertion into a peripheral vein and placement in the central venous system, where it will be exposed to all the blood returning to the heart. The PRAC will incorporate a cylindrical bundle of microporous hollow fiber membranes woven as a fabric that is wrapped around a balloon. The balloon is pulsed with helium and enhances gas exchange by pumping blood past the hollow fibers at velocities much greater than would otherwise exist in the vena cava. The specific aims of the project are to: 1. Fabricate candidate PRAC devices with insertional diameters of 25-28 Fr (8-9 mm) and evaluate the functional mass transfer characteristics in an in-vitro test loop. We will establish how the gas exchange performance of the PRAC depends on key operating and design parameters. 2. Evaluate and optimize balloon pulsation in the PRAC to improve gas exchange. We will principally explore changes in balloon geometry and balloon pulsation mode, and we will use flow visualization, local gas tension measurements, and computational simulations to help guide our design development. 3. Perform acute calf implants of the PRAC to assess the gas exchange functionality in-situ and any adverse anatomical, physiological and biocompatibility effects associated with short- term implantation. We will also evaluate the hemolysis potential of candidate PRAC designs in-vitro using bovine blood in a bench flow loop. Our target is a percutaneous assist catheter that can provide 75- 85 ml/min of extrapulmonary CO2 removal at normocapnia and that could be used as an adjuvant or replacement to existing therapy for patients with acute lung failure (ARDS, pneumonia) or acute on chronic lung failure (COPD with exacerbation).